The present invention relates to improving the precision and/or accuracy of fluids aspirated or dispensed. In particular, the present invention relates to automated diagnostic analyzers having improved aspirate or dispense accuracy and/or precision. The present invention also relates to having improved sensitivity/specificity in detecting failure modes.
Known diagnostic analyzers include immunodiagnostic analyzers such as the Vitros® ECi immunodiagnostic analyzer, or clinical chemistry analyzers such as the Vitros® 5.1 FS, both sold by Ortho-Clinical Diagnostics, Inc. All such analyzers are collectively called diagnostic analyzers. Such systems rely on the assurance that a proper sample volume and/or reagent will be delivered in order to give a precise reported assay result. The precision and/or accuracy of delivered fluid volumes are typically known and often a significant contributor to the precision and accuracy of reported results.
Another problem in providing precise and accurate reported assay results are failure modes. Such failure modes can include clots, excessively high viscosity and bubbles, all of which can cause imprecision and inaccuracy in delivered fluid volumes. Typically, when a failure mode is detected, the reported result is suppressed or the process is aborted, and another assay must be carried out at the expense of additional sample, reagents and time. Some diagnostic analyzers use pressure detection systems to monitor the aspiration and dispense of sample and reagent liquids. However, many analyzers use flow-based systems and sensors other than pressure sensors to monitor flow rate for aspirating and dispensing a fluid. Based on research and math models it has been determined that electrical signals for flow monitoring within incompressible fluids creates a significant amount of noise and are not robust for failure detection. Pressure monitoring of compressible fluids and vision based monitoring systems yield more reliable failure detection capabilities.
In an attempt to conserve sample volume, especially in pediatric and geriatric settings, and in an attempt to minimize reagent usage for cost consideration, test volumes are under constant pressure to be reduced. As volumes are reduced below 5 μL, liquid handling system requirements for precision and accuracy are becoming more stringent. Small deviations in delivered volume of liquid have a direct affect on the reaction and result. Some known art describes detecting liquid handling error modes such as bubbles, clots and foam as well as predicting that an aspirated volume is insufficient to allow reporting of a result. See, e.g., U.S. Pat. Nos. 6,060,320, 6,422,431, 6,083,762, 6,220,075, 6,094,966, 5,927,547, 6,079,283 and 6,203,759, which all disclose aspirating and/or dispensing liquids using an aspirate/dispense probe. EP 608425 discloses a device for measuring viscosity of liquids. U.S. Pat. No. 5,257,529 discloses a method and device for the measurement of viscosity of liquids. WO 94/23280 discloses a method for the measurement of the surface tension of biological fluids. U.S. Pat. No. 4,165,632 discloses a method and apparatus for measuring the fluidity of liquids. U.S. Pat. No. 5,494,639 discloses a biosensor for measuring changes in viscosity and/or density of a fluid.
For the foregoing reasons, there is a need for a method of metering a liquid that can sense and correct for variations in the volume of a metered liquid, and hence, more accurately estimate the actual volume of metered liquid. There is also a need for a method that can accurately detect failure modes in a metered fluid.